Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility

细菌性阴道病引起的阴道 T 细胞表型变化及其对 HIV 易感性的影响

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作者:Finn MacLean, Adino Tesfahun Tsegaye, Jessica B Graham, Jessica L Swarts, Sarah C Vick, Nicole Potchen, Irene Cruz Talavera, Lakshmi Warrier, Julien Dubrulle, Lena K Schroeder, Corinne Mar, Katherine K Thomas, Matthias Mack, Michelle C Sabo, Bhavna H Chohan, Kenneth Ngure, Nelly Mugo, Jairam R Linga

Abstract

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent in reproductive-age women worldwide. Adverse outcomes associated with BV include an increased risk of sexually acquired Human Immunodeficiency Virus (HIV), yet the immunological mechanisms underlying this association are not well understood. To investigate BV driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and peripheral blood mononuclear cells (PBMC). Immunofluorescence analysis of genital mucosal tissues revealed a reduced density of CD3+CD4+CCR5+ cells in the VT lamina propria of individuals with compared to those without BV (median 243.8 cells/mm2 BV- vs 106.9 cells/mm2 BV+, p=0.043). High-parameter flow cytometry of VT biopsies revealed an increased frequency in individuals with compared to those without BV of dysfunctional CD39+ conventional CD4+ T cells (Tconv) (median frequency 15% BV- vs 30% BV+, padj=0.0331) and tissue-resident CD69+CD103+ Tconv (median frequency 24% BV- vs 38% BV+, padj=0.0061), previously reported to be implicated in HIV acquisition and replication. Our data suggests that BV elicits diverse and complex VT T cell alterations and expands on potential immunological mechanisms that may promote adverse outcomes including HIV susceptibility.

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